Physiological characterization of taxol-induced large-fiber sensory neuropathy in the rat

Kenneth D. Cliffer, Judith A. Siuciak, Susan R. Carson, Heather E. Radley, John S. Park, Dacie R. Lewis, Elizabeth Zlotchenko, Trang Nguyen, Karen Garcia, James R. Tonra, Nancy Stambler, Jesse M. Cedarbaum, Sue C. Bodine, Ronald M. Lindsay, Peter S. DiStefano

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

The cancer chemotherapeutic agent Taxol (paclitaxel) causes a dose- related peripheral neuropathy in humans. We produced a dose-dependent large- fiber sensory neuropathy, without detrimental effects on general health, in mature rats by using two intravenous injections 3 days apart. Tests of other dosing schedules demonstrated the dependence of the severity of the neuropathy and of animal health on both the dose and the frequency of dosing. Pathologically, severe axonal degeneration and hypomyelination were observed in sections of dorsal roots, whereas ventral roots remained intact. Electrophysiologically, H-wave amplitudes in the hindlimb and amplitudes of predominantly sensory compound nerve action potentials in the tail were reduced. These effects persisted for at least 4 months after treatment. Motor amplitudes were not affected, but both motor and sensory conduction velocities decreased. The ability of rats to remain balanced on a narrow beam was impaired, indicating proprioceptive deficits. Muscle strength, measured by hindlimb and forelimb grip strength, and heat nociception, measured by tail-flick and hindlimb withdrawal tests, were not affected by Taxol. This model of Taxol-induced neuropathy in mature rats, with minimal effects on general health, parallels closely the clinical syndrome observed after Taxol treatment in humans.

Original languageEnglish (US)
Pages (from-to)46-55
Number of pages10
JournalAnnals of Neurology
Volume43
Issue number1
DOIs
StatePublished - Jan 1998
Externally publishedYes

Fingerprint

Paclitaxel
Hindlimb
Spinal Nerve Roots
Tail
Health
Aptitude
Nociception
Forelimb
Muscle Strength
Hand Strength
Peripheral Nervous System Diseases
Intravenous Injections
Action Potentials
Appointments and Schedules
Hot Temperature
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cliffer, K. D., Siuciak, J. A., Carson, S. R., Radley, H. E., Park, J. S., Lewis, D. R., ... DiStefano, P. S. (1998). Physiological characterization of taxol-induced large-fiber sensory neuropathy in the rat. Annals of Neurology, 43(1), 46-55. https://doi.org/10.1002/ana.410430111

Physiological characterization of taxol-induced large-fiber sensory neuropathy in the rat. / Cliffer, Kenneth D.; Siuciak, Judith A.; Carson, Susan R.; Radley, Heather E.; Park, John S.; Lewis, Dacie R.; Zlotchenko, Elizabeth; Nguyen, Trang; Garcia, Karen; Tonra, James R.; Stambler, Nancy; Cedarbaum, Jesse M.; Bodine, Sue C.; Lindsay, Ronald M.; DiStefano, Peter S.

In: Annals of Neurology, Vol. 43, No. 1, 01.1998, p. 46-55.

Research output: Contribution to journalArticle

Cliffer, KD, Siuciak, JA, Carson, SR, Radley, HE, Park, JS, Lewis, DR, Zlotchenko, E, Nguyen, T, Garcia, K, Tonra, JR, Stambler, N, Cedarbaum, JM, Bodine, SC, Lindsay, RM & DiStefano, PS 1998, 'Physiological characterization of taxol-induced large-fiber sensory neuropathy in the rat', Annals of Neurology, vol. 43, no. 1, pp. 46-55. https://doi.org/10.1002/ana.410430111
Cliffer KD, Siuciak JA, Carson SR, Radley HE, Park JS, Lewis DR et al. Physiological characterization of taxol-induced large-fiber sensory neuropathy in the rat. Annals of Neurology. 1998 Jan;43(1):46-55. https://doi.org/10.1002/ana.410430111
Cliffer, Kenneth D. ; Siuciak, Judith A. ; Carson, Susan R. ; Radley, Heather E. ; Park, John S. ; Lewis, Dacie R. ; Zlotchenko, Elizabeth ; Nguyen, Trang ; Garcia, Karen ; Tonra, James R. ; Stambler, Nancy ; Cedarbaum, Jesse M. ; Bodine, Sue C. ; Lindsay, Ronald M. ; DiStefano, Peter S. / Physiological characterization of taxol-induced large-fiber sensory neuropathy in the rat. In: Annals of Neurology. 1998 ; Vol. 43, No. 1. pp. 46-55.
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